Project Summary The Bloomington Drosophila Stock Center (BDSC) supports a large, worldwide community of scientists using the insect Drosophila melanogaster as a model organism for biomedical experimentation. Its primary missions are to provide a collection of documented living stocks of broad value to current research, to preserve documented strains with clear future value, and to provide information and support services that promote maximal exploitation of these materials. The goal of this revision proposal is to continue making a large set of Drosophila strains available through the BDSC for the controlled expression of any UAS-based genetic construct in a small subset of cells defined by the intersecting expression patterns of two ?split-GAL4? driver constructs. In the split-GAL4 system, one driver construct expresses the GAL4 DNA-binding domain fused to a protein-pairing domain and the other construct produces a transcriptional activation domain fused to the complementary protein pairing domain. In cells where the expression patterns of the two drivers coincide, dimerization can occur to generate an active GAL4 and UAS transgenes can be expressed. This intersectional strategy produces more refined and specific expression patterns than those produced by single drivers. This system has been used to define and manipulate the functions of specific neuron types in investigations of brain wiring and it has the potential to identify unique subsets of cells in many other tissues and allow them to be manipulated experimentally. The funding proposed here would make it possible for the BDSC to continue maintaining, distributing and promoting the use of an extensive set of stocks with split-GAL4 transgenes, which were generated at considerable effort and cost by investigators at Janelia Research Campus and were transferred to the BDSC for distribution under an administrative supplement in September 2017. Funding will make this large collection available to the full biomedical research community and will provide new opportunities to identify cell populations, explore their functions and use them in developing models of human disease processes.